Hybrid Mice as Genetic Models of High Alcohol Consumption
- 151 Downloads
We showed that F1 hybrid genotypes may provide a broader variety of ethanol drinking phenotypes than the inbred progenitor strains used to create the hybrids (Blednov et al. in Alcohol Clin Exp Res 29:1949–1958, 2005). To extend this work, we characterized alcohol consumption as well as intake of other tastants (saccharin, quinine and sodium chloride) in five inbred strains of mice (FVB, SJL, B6, BUB, NZB) and in their reciprocal F1 hybrids with B6 (FVBxB6; B6xFVB; NZBxB6; B6xNZB; BUBxB6; B6xBUB; SJLxB6; B6xSJL). We also compared ethanol intake in these mice for several concentrations before and after two periods of abstinence. F1 hybrid mice derived from the crosses of B6 and FVB and also B6 and SJL drank higher levels of ethanol than their progenitor strains, demonstrating overdominance for two-bottle choice drinking test. The B6 and NZB hybrid showed additivity in two-bottle choice drinking, whereas the hybrid of B6 and BUB demonstrated full or complete dominance. Genealogical origin, as well as non-alcohol taste preferences (sodium chloride), predicted ethanol consumption. Mice derived from the crosses of B6 and FVB showed high sustained alcohol preference and the B6 and NZB hybrids showed reduced alcohol preference after periods of abstinence. These new genetic models offer some advantages over inbred strains because they provide high, sustained, alcohol intake, and should allow mapping of loci important for the genetic architecture of these traits.
KeywordsAlcohol intake Inbred strains F1 hybrid Tastes Overdominance
This study or research was supported by grants from the National Institute of Alcohol Abuse and Alcoholism (AA U01 13520 and AA U01 AA016655—INIA West Projects), NIH A06399 and AA01760, and SRCS Award from the Department of Veterans Affairs. The authors would like to thank Virginia Bleck for excellent technical assistance.
- Falconer DS, Mackay TFC (1996) Introduction to quantitative genetics, 4th edn. Longman, EssexGoogle Scholar
- Festing MFW (1994) Inbred strains of mice. Mouse Genome 92:420–426Google Scholar
- Kearsey MJ, Pooni HS (1996) The genetical analysis of quantitative traits. Chapman and Hall, LondonGoogle Scholar
- Morse HC III (1978) Origins of inbred mice. Academic Press, New YorkGoogle Scholar
- Petkov PM, Ding Y, Cassell MA, Zhang W, Wagner G, Sargent EE, Asquith S, Crew V, Johnson KA, Robinson P, Scott VE, Wiles MV (2004) An efficient SNP system for mouse genome scanning and elucidating strain relationships. Genome Res 14:1806–1811Google Scholar
- Rodgers DA (1972) Factors underlying differences in alcohol preference in inbred strains of mice. In: Kissin B, Begleiter H (eds) The biology of alcoholism. Plenum, New York, pp 107–130Google Scholar
- Rosenthal R (1994) Parametric measures of effect size. In: Cooper H, Hedges LV (eds) The handbook of research synthesis. Russell Sage Foundation, New York, pp 231–244Google Scholar
- Shull GH (1948) What is heterosis? Genetics 33:439–446Google Scholar